SPY002-091 Safety Study in Healthy Volunteers

Overseen By Medical Director, Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Spyre Therapeutics, Inc.

Disqualifiers: Drug abuse, Alcoholism, Smoking, others

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

56 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy volunteers, it's likely that participants should not be on any regular medications. Please check with the study coordinators for more details.

What safety data exists for SPY002-091 or similar treatments in healthy volunteers?

In studies involving healthy volunteers, adverse events like headache, drowsiness, and weakness were reported during placebo administration, with an overall incidence of 19%. These findings highlight the importance of considering experimental conditions when evaluating safety in clinical trials. ^{1 2 3 4 5}

How is the drug SPY002-091 different from other treatments?

SPY002-091 is unique because it is being tested in healthy volunteers at very low doses (microdoses) to assess its safety and metabolism early in the drug development process, which helps minimize animal testing and provides early human data. ^{1 6 7 8 9}

What is the purpose of this trial?

This is a Phase 1, randomized, double-blind, placebo-controlled, single- dose, first in human safety, tolerability, and pharmacokinetic study of SPY002-091 in healthy participants.

Research Team

Joshua Friedman, MD

Principal Investigator

Spyre Therapeutics

Eligibility Criteria

This clinical trial is open to healthy men and women who can commit to the study schedule, including staying at the research site when needed. People with a history of drug abuse, heavy alcohol use, smoking recently, or significant health issues cannot participate.

Inclusion Criteria

I am a healthy man or woman.

I can attend all required study visits and stay at the study site when needed.

Exclusion Criteria

Participation in more than one cohort

Evidence of clinically significant abnormality or disease

I have not used illegal drugs, abused alcohol, or used nicotine products in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single ascending dose of SPY002-091 or placebo

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

Treatment Details

Interventions

• Placebo
• SPY002-091

Trial Overview The study is testing SPY002-091 in its first human trial. It's a Phase 1 trial where participants are randomly given either SPY002-091 or a placebo without knowing which one they receive to evaluate safety, tolerability, and how the body processes it.

Participant Groups

Group I: SAD Cohorts, Experimental Arm Experimental Treatment 1 Intervention

Participants will receive a single dose of SPY002-091 in a dose escalation format

Group II: SAD Cohorts, Placebo Arm Placebo Group 1 Intervention

Participants will receive a single dose of placebo

Who Is Running the Clinical Trial?

Spyre Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

270+

Altasciences Company Inc.

Industry Sponsor

Trials

18

Recruited

860+

Findings from Research

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

In a five-year analysis of 1,559 healthy volunteers across 142 phase I studies, the overall incidence of adverse events (AEs) was 8.8%, with most AEs being mild or moderate in severity, indicating that while AEs are common, they are generally not severe.

The incidence of AEs was significantly higher in multiple-dose studies compared to single-dose trials, highlighting the importance of study design in assessing the safety profile of active drugs, with a notable increase in AEs on the first day of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. Lutfullin, A., Kuhlmann, J., Wensing, G.[2019]

Adverse events (AEs) are reported in 49.1% of trial participants in placebo groups, indicating that these events are quite common and not solely due to the natural progression of conditions.

The prevalence of AEs in placebo groups (6.51%) is higher than in untreated groups (4.25%), suggesting that the nocebo effect may play a significant role in the experience of AEs during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Howick, J., Webster, R., Kirby, N., et al.[2022]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

In a review of 24 First-in-Man studies involving 1,017 healthy male volunteers, the incidence of adverse events (AEs) was low, with 98.3% of AEs being mild or moderate, indicating a favorable safety profile for small molecules in Phase I trials.

Only 0.4% of treatments resulted in serious adverse events, all of which were not medically concerning and did not require hospitalization, suggesting that small molecule trials can be conducted safely in healthy volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of healthy volunteers in First-in-Man trials - an analysis of studies conducted at the Bayer in-house ward from 2000 to 2005. Wensing, G., Ighrayeb, IA., Boix, O., et al.[2019]

A ten-day trial demonstrated a significant reduction in viral load among volunteers, indicating potential efficacy of the treatment being tested.

The results suggest that the intervention may effectively lower the amount of virus present in the body, which is crucial for managing viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrase inhibitors: first clear success in human trial. James, JS.[2016]

The workshop highlighted the potential of using very low dose human studies (microdoses) to assess drug candidates earlier in the development process, which could improve the selection of effective drugs while ensuring volunteer safety.

Incorporating advanced techniques like accelerator mass spectrometry (AMS) and positron emission tomography (PET) in these early human studies could provide valuable data on how drugs are processed in the body, potentially reducing reliance on animal testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. Combes, RD., Berridge, T., Connelly, J., et al.[2019]

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

The safety of healthy volunteers in First-in-Man trials - an analysis of studies conducted at the Bayer in-house ward from 2000 to 2005. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Integrase inhibitors: first clear success in human trial. [2016]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. [2019]